Distinct mesoscale cortical dynamics encode search strategies during spatial navigation.

Spatial navigation is a complex cognitive process that involves neural computations in distributed regions of the brain. Little is known about how cortical regions are coordinated when animals navigate novel spatial environments or how that coordination changes as environments become familiar. We recorded mesoscale calcium (Ca) dynamics across large swathes of the dorsal cortex in mice solving the Barnes maze, a 2D spatial navigation task where mice used random, serial, and spatial search strategies to navigate to the goal. Cortical dynamics exhibited patterns of repeated calcium activity with rapid and abrupt shifts between cortical activation patterns at sub-second time scales. We used a clustering algorithm to decompose the spatial patterns of cortical calcium activity in a low dimensional state space, identifying 7 states, each corresponding to a distinct spatial pattern of cortical activation, sufficient to describe the cortical dynamics across all the mice. When mice used serial or spatial search strategies to navigate to the goal, the frontal regions of the cortex were reliably activated for prolonged durations of time (> 1s) shortly after trial initiation. These frontal cortex activation events coincided with mice approaching the edge of the maze from the center and were preceded by temporal sequences of cortical activation patterns that were distinct for serial and spatial search strategies. In serial search trials, frontal cortex activation events were preceded by activation of the posterior regions of the cortex followed by lateral activation of one hemisphere. In spatial search trials, frontal cortical events were preceded by activation of posterior regions of the cortex followed by broad activation of the lateral regions of the cortex. Our results delineated cortical components that differentiate goal- and non-goal oriented spatial navigation strategies.